Project 2, which will be new to the UW SBRP, is an epidemiologic investigation of the roles of metals as determinants of the risk, severity, and progression of parkinsonism (PS) among professional welders. Previous epidemiologic and experimental research has demonstrated very plausible links between manganese (Mn) and other metals, individually and in combination, and PS. The study population includes 875 Wisconsin shipyard welders (775 actively employed, 100 retired) and 200 non-exposed shipyard workers with no welding exposure history previously enrolled in an ongoing NEIHS-funded R01 (ES013743;PI: B. Racette;Co-investigators: H. Checkoway, N. Seixas). The new features of this proposed study will be the refinement of exposure assessment to generate quantitative metal-specific levels, and repeated neurological examinations of longitudinal change of PS-related motor function. The scientific objectives of the project are to: 1) estimate dose-response relations between Mn and other metal exposures and PS risk and severity;2) test the hypothesis that these metal exposures are associated with PS progression;3) determine the predictive relations of PS proteomic biomarkers, characterized in Project 3 (Dr. Zhang), with PS risk, severity, and progression;4) test dose-response relations for Mn and other metals with PS proteomic biomarker profiles as indicators of preclinical disease. To achieve these objects, we will perform repeated standardized neurological exams of motor function (Unified Parkinson's Disease Rating Scale Motor Subsection 3 [UPDRS3]) 3 years after enrollment exams for as many study subjects as can be enrolled (~75%). Addionally, in collaboration with Project 3, we will collect plasma samples for assays of proteomics that have been validated as strongly associated with PS for a sample of 150 subjects selected according to baseline UPDRS3 ('normal', borderline PS, probable/definite PS). Data on potentially important confounding factors, especially cigarette smoking and pesticide exposure, will be obtained by questionnaire. This project has great potential to quantify the extent of neurological effects of metals, which are widespread environmental contaminants, and thus could contribute to disease prevention strategies.
Manganese (Mn) and other metals are widespread environmental contaminants, and have been linked with adverse neurological effects, especially parkinsonism (PS). This study will investigate epidemiologic associations between these metals and risk, severity, and progression of PS among professional welders. The findings have great potential to generate important new knowledge for disease prevention.
|Ma, Eva Y; Heffern, Kevin; Cheresh, Julia et al. (2018) Differential copper-induced death and regeneration of olfactory sensory neuron populations and neurobehavioral function in larval zebrafish. Neurotoxicology 69:141-151|
|Heffern, Kevin; Tierney, Keith; Gallagher, Evan P (2018) Comparative effects of cadmium, zinc, arsenic and chromium on olfactory-mediated neurobehavior and gene expression in larval zebrafish (Danio rerio). Aquat Toxicol 201:83-90|
|Racette, Brad A; Gross, Anat; Criswell, Susan R et al. (2018) A screening tool to detect clinical manganese neurotoxicity. Neurotoxicology 64:12-18|
|Barrett, P M; Hull, E A; King, C E et al. (2018) Increased exposure of plankton to arsenic in contaminated weakly-stratified lakes. Sci Total Environ 625:1606-1614|
|Rooney, James P K; Woods, Nancy F; Martin, Michael D et al. (2018) Genetic polymorphisms of GRIN2A and GRIN2B modify the neurobehavioral effects of low-level lead exposure in children. Environ Res 165:1-10|
|Chang, Yu-Chi; Cole, Toby B; Costa, Lucio G (2018) Prenatal and early-life diesel exhaust exposure causes autism-like behavioral changes in mice. Part Fibre Toxicol 15:18|
|Criswell, Susan R; Nielsen, Susan Searles; Warden, Mark et al. (2018) [18F]FDOPA positron emission tomography in manganese-exposed workers. Neurotoxicology 64:43-49|
|Wang, Hao; Zhang, Liang; Abel, Glen M et al. (2018) Cadmium Exposure Impairs Cognition and Olfactory Memory in Male C57BL/6 Mice. Toxicol Sci 161:87-102|
|Criswell, Susan R; Warden, Mark N; Searles Nielsen, Susan et al. (2018) Selective D2 receptor PET in manganese-exposed workers. Neurology 91:e1022-e1030|
|Meador, James P; Yeh, Andrew; Gallagher, Evan P (2018) Adverse metabolic effects in fish exposed to contaminants of emerging concern in the field and laboratory. Environ Pollut 236:850-861|
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